Each year, 70,000 patients in the United States need to have their diseased heart valves replaced. These patients can receive either bioprostheses made from animal tissues, or mechanical valves made from synthetic materials. Bioprostheses have few complications and are considered the ideal valve for most patients, but ultimately wear out last only about 12-15 years. Mechanical valves, on the other hand, because anticoagulation-related complications and used only if the patient is too young to receive a bioprosthesis. The issue that drives the decision for a mechanical or bioprosthetic valve is the risk of reoperation - prosthetic valves are intended to be implanted once and should last the life of the patient. To address the problem of reoperative mortality, VXI has been developing an alternative approach - a rapidly exchangeable bioprosthetic valve. It is a two-component device, consisting of a permanent "docking station" that remains affixed to the patient's aorta, and a collapsible frame that supports the exchangeable leaflet set and plugs into the docking station. Exchange can be done quickly and safely, using minimally invasive tools or catheters, eliminating most of the risk of reoperation. With this technology, there is finally a tissue valve for mechanical valve patients. In an effort to broaden the use of the exchangeable valve technology, VXI is addressing an emerging technology - heart valve tissue engineering. Progress in this field has been hampered by the cost of the experimental model - the juvenile sheep that has a tissue-engineered valve implanted in the aortic position. At about $15,000 per experiment, scientists need to minimize the number of sheep and maximize the duration of the implant period. This approach limits the information that can be obtained from such experiments. If the animal experiments were to use an exchangeable valve, such as that developed by VXI, the animal need not be sacrificed. The valve can be explanted, examined, re-implanted, or exchanged with a different tissue-engineered valve, without needing to sacrifice the animal. The objectives of this STTR proposal, therefore, are to (i) develop an exchangeable valve that can be fitted with leaflets composed biodegradable polymers typically used for tissue engineering, and (ii) evaluate the integrity of the tissue ingrowth into the exchangeable frame through tissue culture and mechanical testing. Hydrodynamic durability testing will also be done to (iii) ensure that there are no design flaws in the complete valve assembly. Through this project, VXI will develop technologies that will serve the basic scientist engaged in tissue engineering. VXI will thus continue to advance the field of prosthetic valve technologies into new areas where innovative solutions for patients with heart valve disease are needed. Each year, 70,000 patients in the United States need to have their diseased heart valves replaced. These patients can receive valves made from animal tissues, or synthetic, man- made materials. Tissue valves have few complications and are considered the ideal valve for most patients, but ultimately wear out in about 12-15 years. Mechanical valves, on the other hand, cause blood clotting problems and the patients need to be on permanent blood thinners, essentially living the life of a hemophiliac. The issue that drives the decision for a synthetic or tissue-based valve is the risk of reoperation. Although the first open- heart surgery is relatively safe, subsequent surgeries are far more risky. Artificial heart valves are intended to be implanted once and should last the life of the patient. To address the problem of reoperative complications, VXI has been developing an alternative approach - a rapidly exchangeable tissue valve. It is a two-component device, consisting of a permanent "docking station" that remains in the patient, and a collapsible frame that supports the exchangeable tissue that ultimately wears out. This exchangeable component snaps in and out from the docking station. The procedure to exchange the valve can be done quickly and safely, without requiring open-heart surgery. In an effort to broaden the use of the exchangeable valve technology, VXI is addressing an emerging technology - heart valve tissue engineering. Progress in this field has been hampered by the cost of the animal experiments in which the feasibility of this approach always needs to be demonstrated. The most commonly used animal model is a juvenile sheep, which has prototype tissue tissue-engineered valves surgically implanted. After 6- 9 months, the animal is killed and the valve removed and examined for re-growth and healing. Since each experiment costs about $15,000, including the surgery, scientists need to minimize the number of sheep used and maximize the duration of the experiment. This approach, however, limits the information that can be obtained from such experiments. If the animal experiments were to use an exchangeable valve, such as that developed by VXI, the animal need not be sacrificed. The valve can be removed, examined, re-implanted, or exchanged with a different tissue-engineered valve, without needing to kill the animal. The objectives of this STTR proposal, therefore, are to (i) develop an exchangeable valve that can be fitted with leaflets composed biodegradable polymers typically used for tissue engineering, and (ii) evaluate the integrity of the tissue in-growth into the exchangeable valve frame through tissue culture and mechanical testing. Durability testing will also be done to (iii) ensure that there are no design flaws in the complete valve assembly. Through this project, VXI will develop technologies that will benefit scientists developing tissue-engineered heart valves. VXI will thus continue to advance the field of heart valve technologies into new areas where innovative solutions for patients with heart valve disease are needed. [unreadable] [unreadable] [unreadable]